Preparation, characterization and application of long-acting FSH analogs for assisted reproduction

Ben-Menahem, David

doi:10.1016/j.theriogenology.2017.08.020

Cited by 11 publications

(4 citation statements)

References 110 publications

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“…In addition, the molecular weight of the reassembled rhFSH-G (about 40 kDa) and rhFSH-M (about 40 kDa) was found to be slightly larger than that of natural hFSH (about 32 kDa), which is partially due to the glycosylation and addition of signal peptide of the subunits. Previous studies demonstrated that increasing molecular weight and charge of FSH by additional glycosylation might prolong its half-life by reducing the glomerular filtration of FSH . Our results suggested that the relative increase of the average elimination half-life ( t 1/2 ) of reassembled rhFSH-G and rhFSH-M to that of Gonal-F might be due to the extra glycosylation.…”

Section: Discussionsupporting

confidence: 48%

“…Previous studies demonstrated that increasing molecular weight and charge of FSH by additional glycosylation might prolong its half-life by reducing the glomerular filtration of FSH. 47 Our results suggested that the relative increase of the average elimination half-life (t 1/2 ) of reassembled rhFSH-G and rhFSH-M to that of Gonal-F might be due to the extra glycosylation.…”

Section: ■ Discussionmentioning

confidence: 62%

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Novel Functional Recombinant Human Follicle-Stimulating Hormone Acquired from Goat Milk

Hua

Liu

et al. 2021

J. Agric. Food Chem.

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An animal mammary bioreactor is regarded as an excellent biological system which is applied to produce large-scale recombinant proteins in milk. However, there are no effective methods to produce a large amount of some pharmaceutical proteins, such as human follicle-stimulating hormone (FSH), by large animal mammary gland bioreactors due to the fact that accumulation of excessive bioactive FSH might cause serious diseases in animals. Here, we report a novel strategy of preparing recombinant human FSH (rhFSH) from goat mammary glands, which could avoid the accumulation of bioactive FSH in goats. First, the single inactive FSHα and FSHβ subunits expressed in goat mammary epithelial cells and goat mammary glands were performed to reassemble in vitro and were found to self-assemble into a complete heterodimer rhFSH at 4 °C and pH 7.4. Further, a cyclic adenosine monophosphate (cAMP) induction assay showed that the cAMP levels in cell lysate of HEK 293/FSHR cells were increased by about 8-fold in reassembled rhFSH groups than that in the control group (P < 0.01). Pharmacokinetic analysis indicated that the reassembled rhFSH from goat mammary glands was comparable to that of the commercially available Gonal-F (P > 0.05). In addition, the increasing dose of reassembled rhFSH significantly promoted ovulation of mouse and ovary weight gain of Sprague Dawley rat compared with the control groups and maximum values were up to 3-fold (P < 0.01) and 2.8-fold (P < 0.01), respectively. The reassembled rhFSH showed a similar effect to Gonal-F in inducing expression of FSH target genes in vivo and activating the PI3K pathway in granulosa cells. Our study developed a novel method to produce rhFSH and provided the basis for preparing FSH by the goat mammary gland bioreactor with less health problems on the producing animals.

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Section: Discussionsupporting

confidence: 48%

Section: ■ Discussionmentioning

confidence: 62%

Novel Functional Recombinant Human Follicle-Stimulating Hormone Acquired from Goat Milk

Hua

Liu

et al. 2021

J. Agric. Food Chem.

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“…In males, the FSH binds to FSHR on the Sertoli cells and regulates their proliferation and spermatogenesis [ 5 , 6 , 7 ]. The exogenous FSH is widely used for the treatment of anovulation and in assisted reproduction technologies [ 8 , 9 , 10 ]. The exogenous FSH is currently either purified from human urine or the recombinant FSH (rFSH) is produced by recombinant DNA technology [ 8 ], although both sources have several limitations [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…The exogenous FSH is widely used for the treatment of anovulation and in assisted reproduction technologies [ 8 , 9 , 10 ]. The exogenous FSH is currently either purified from human urine or the recombinant FSH (rFSH) is produced by recombinant DNA technology [ 8 ], although both sources have several limitations [ 11 , 12 , 13 ]. Therefore, there is an impetus to develop functional alternatives.…”

Section: Introductionmentioning

confidence: 99%

Two Synthetic Peptides Corresponding to the Human Follicle-Stimulating Hormone β-Subunit Promoted Reproductive Functions in Mice

Han

Bai

Yao

et al. 2022

IJMS

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A follicle stimulating hormone (FSH) is widely used in the assisted reproduction and a synthetic peptide corresponding to a receptor binding region of the human (h) FSH-β-(34–37) (TRDL) modulated reproduction. Furthermore, a 13-amino acid sequence corresponding to hFSH-β-(37–49) (LVYKDPARPKIQK) was recently identified as the receptor binding site. We hypothesized that the synthetic peptides corresponding to hFSH-β-(37–49) and hFSH-β-(34–49), created by merging hFSH-β-(34–37) and hFSH-β-(37–49), modulate the reproductive functions, with the longer peptide being more biologically active. In male or female prepubertal mice, a single injection of 200 μg/g BW ip of hFSH-β-(37–49) or hFSH-β-(34–49) hastened (p < 0.05) puberty, whereas the same treatments given daily for 4 d promoted (p < 0.05) the gonadal steroidogenesis and gamete formation. In addition of either peptide to the in vitro cell cultures, promoted (p < 0.05) the proliferation of primary murine granulosa cells and the estradiol production by upregulating the expression of Ccnd2 and Cyp19a1, respectively. In adult female mice, 200 μg/g BW ip of either peptide during diestrus antagonized the FSH-stimulated estradiol increase and uterine weight gain during proestrus. Furthermore, hFSH-β-(34–49) was a more potent (p < 0.05) reproductive modulator than hFSH-β-(37–49), both in vivo and in vitro. We concluded that hFSH-β-(37–49) and especially hFSH-β-(34–49), have the potential for reproductive modulation.

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Hormones, Blood Products, and Therapeutic Enzymes

Silva

Costa

Almeida

et al. 2019

Current Applications of Pharmaceutical Biotechnology

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Preparation, characterization and application of long-acting FSH analogs for assisted reproduction

Cited by 11 publications

References 110 publications

Novel Functional Recombinant Human Follicle-Stimulating Hormone Acquired from Goat Milk

Novel Functional Recombinant Human Follicle-Stimulating Hormone Acquired from Goat Milk

Two Synthetic Peptides Corresponding to the Human Follicle-Stimulating Hormone β-Subunit Promoted Reproductive Functions in Mice

Hormones, Blood Products, and Therapeutic Enzymes

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